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      Mycophenolate versus Cyclophosphamide for Lupus Nephritis

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          Abstract

          Systemic lupus erythematosus is common in our country, and renal involvement is an important cause of chronic kidney disease. This study was aimed at comparing the three regimens, i.e., cyclophosphamide-based regimes (low dose and high dose) and mycophenolate mofetil (MMF)-based regime and determining if cyclophosphamide (CPM)-based regime can be an effective, safe, and cheap alternative to MMF-based regime in a resource-limited setting. Out of 144 patients, females constituted 89%. Nephrotic nephritic presentation was the most common. Rapidly progressive renal failure was seen in in 42 (29.1%) patients. Class IV was the most common 66 (45.8%) histological class. Crescentic glomerulonephritis was seen in 18 (12.5%). Overall remission (complete + partial) at 6 months was seen in 71.4% in National Institute of Health regime, 65% in European lupus nephritis trial protocol and 72.9% in MMF regime. End-stage renal disease and switching to other therapies were comparable among the three groups. Although infections were more with CPM, the difference was not statistically significant. CPM-based therapies were associated with a significantly lower cost.

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          The classification of glomerulonephritis in systemic lupus erythematosus revisited.

          Jan Weening, Vivette D. D'Agati, Melvin M Schwartz … (2004)
          The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving or =50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.
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            Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis.

            Gerald B Appel, Gabriel Contreras, Mary Anne Dooley … (2009)
            Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m(2) in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.
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              Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide.

              Frédéric A. Houssiau, Carlos Silva Vasconcelos, David D'Cruz … (2002)
              Glomerulonephritis is a severe manifestation of systemic lupus erythematosus (SLE) that is usually treated with an extended course of intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen, we evaluated the efficacy and the toxicity of a course of low-dose IV CYC prescribed as a remission-inducing treatment, followed by azathioprine (AZA) as a remission-maintaining treatment. In this multicenter, prospective clinical trial (the Euro-Lupus Nephritis Trial [ELNT]), we randomly assigned 90 SLE patients with proliferative glomerulonephritis to a high-dose IV CYC regimen (6 monthly pulses and 2 quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose IV CYC regimen (6 fortnightly pulses at a fixed dose of 500 mg), each of which was followed by AZA. Intent-to-treat analyses were performed. Followup continued for a median of 41.3 months in the low-dose group and 41 months in the high-dose group. Sixteen percent of those in the low-dose group and 20% of those in the high-dose group experienced treatment failure (not statistically significant by Kaplan-Meier analysis). Levels of serum creatinine, albumin, C3, 24-hour urinary protein, and the disease activity scores significantly improved in both groups during the first year of followup. Renal remission was achieved in 71% of the low-dose group and 54% of the high-dose group (not statistically significant). Renal flares were noted in 27% of the low-dose group and 29% of the high-dose group. Although episodes of severe infection were more than twice as frequent in the high-dose group, the difference was not statistically significant. The data from the ELNT indicate that in European SLE patients with proliferative lupus nephritis, a remission-inducing regimen of low-dose IV CYC (cumulative dose 3 gm) followed by AZA achieves clinical results comparable to those obtained with a high-dose regimen.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Indian J Nephrol
                Journal ID (iso-abbrev): Indian J Nephrol
                Journal ID (publisher-id): IJN
                Title: Indian Journal of Nephrology
                Publisher: Medknow Publications & Media Pvt Ltd (India )
                ISSN (Print): 0971-4065
                ISSN (Electronic): 1998-3662
                Publication date (Print): Jan-Feb 2018
                Volume: 28
                Issue: 1
                Pages: 35-40
                Affiliations
                [1] Department of Nephrology, Osmania General Hospital, Hyderabad, Telangana, India
                Author notes
                Address for correspondence: Dr. M. Sahay, 6-3-852/A, Ameerpet, Hyderabad - 500 016, Telangana, India. E-mail: drmanishasahay@ 123456gmail.com
                Article
                Publisher ID: IJN-28-35
                DOI: 10.4103/ijn.IJN_2_16
                PMC ID: 5830807
                PubMed ID: 29515299
                SO-VID: 20bb799f-a3ad-436e-9f0e-43f1ec57a7c6
                Copyright © Copyright: © 2018 Indian Journal of Nephrology
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

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                Subject: Original Article

                ScienceOpen disciplines: Nephrology
                Keywords: cyclophosphamide,induction,lupus nephritis,mycophenolate,systemic lupus erythematous,treatment
                Data availability:
                ScienceOpen disciplines: Nephrology
                Keywords: cyclophosphamide, induction, lupus nephritis, mycophenolate, systemic lupus erythematous, treatment

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